Sonothrombolysis (STL) treatments for acute stroke rely on ultrasound energy (targeting the clot) delivered through the temporal bone and microbubbles injected systemically to achieve clot dissolution and vessel recanalization.
Sonothrombolysis treatments are being investigated by a multitude of researchers and clinicians for their potential role in treating acute stroke. In STL treatments, ultrasound pulses are delivered through the skull temporal bone, targeted at the clot that causes the occlusion. Microbubbles, an ultrasound contrast agent, are introduced into the bloodstream, as their mechanical oscillation at the clot site due to the applied ultrasound energy has been shown to over time dissolve the clot and achieve vessel recanalization for acute stroke treatment. One of the advantages of STL treatments is that they can be performed without the use of drugs (such as t-PA, or tissue plasminogen activator, a common “clotbusting” drug), which carry with them significant restrictions to their use, and overall low treatment success. Circulating microbubbles (which are utilized for the STL treatment), oscillate differently when subjected to different amplitude ultrasound pulses. Such oscillation at higher ultrasound pressures is termed cavitation, which actually emits ultrasound energy as part of this process at many different frequencies (harmonic, subharmonic, and ultraharmonic frequencies), which can be detected.
One challenge associated with STL treatments is that the ultrasound energy is delivered to the clot location inside the patient's brain through the skull. Several acoustic windows are available in the skull that allow ultrasound energy to be transmitted into the brain. For STL, the best acoustic window is the temporal bone, located at the sides and base of the skull, as most strokes occur due to the occlusion of the middle cerebral arteries, which are located behind the temporal bone, and can be visualized with diagnostic ultrasound and color Doppler. Even so, the temporal bone attenuates ultrasound significantly, degrading the ability to image the brain, and also making it more difficult to deliver the required ultrasound energies for successful STL treatments. On average, ultrasound pressures are reduced by 12 dB (75%) by the temporal bone at the 1.6 to 2 MHz frequencies typically being used for STL. This is a significant amount.
Another challenge associated with STL treatments is that the thickness and consequent attenuation of the temporal bone vary from patient to patient, potentially resulting in either higher or lower ultrasound energies being delivered to the clot location, with the potential of causing undesired bioeffects (in the case of a thinner temporal bone yielding higher ultrasound pressures in the brain), or not being able to dissolve the clot at all (in the case of a thicker temporal bone yielding lower ultrasound pressures in the brain).